The ability of cells to discriminate among the myriad of intercellular contacts and to respond selectively is fundamental to the embryogenesis of multicellular organisms. A paradigm of this specificity occurs during the development of the visual projection of lower vertebrates as axons from neural retina form precise, topographically ordered synapse with neurons of the optic tectum. The long-range objective of this research is to understand the mechanisms reponsible for this specificity. In light of the inaccessability and complexity of the in vivo situation the approach outlined here will utilize the observation that retinal neurons adhere in vitro to tectal tissue with topographic selectivity that mimics the neuronal projection. As a working hypothesis, it is assumed that elucidation of the biochemical basis for these adhesive preferences will be relevant to synaptic specificity. Knowledge of the molecules active in the in vitro adhesive systems and special probes such as antibodies may ultimately allow the in vitro mechanism to be tested in the more complex in vivo situation. The proposed research centers on a plasma membrane protein, ligatin, that was recently discovered in ileal epithelial cells where it serves as a baseplate for external cell-surface proteins. Because ligatin is present on the cell surface as a filament, the proteins bound to it are constrained to a regularly arrayed distribution. Our collaborative experiments have shown that ligatin is also a major constituent of plasma membranes in neural retina and that it inhibits the reaggregation of single retinal cells. The experiments proposed here extend these studies and test the hypothesis that retinal ligatin attaches the cell-surface molecules that distinguish cells from different regions of the retina and provide for their intercellular adhesive specificities. In addition, the significance of ligatin's filamentous distribution to questions of adhesion and membrane architecture will be examined.